Table 2.
Pharmacokinetic properties for NS9283 in rats, calculated using WinNonLin non-compartmental analysis
| Strain1and gender | Dose (mg·kg−1) | Route | Cmax2 (ng·mL−1) | Cmax,brain3 (µmol·kg−1tissue) | t½ (h) | AUC∞/D4 (h·ng·mL−1·mg−1·kg) | B/P5 |
|---|---|---|---|---|---|---|---|
| Sprague–Dawley, male | 0.1 | i.p. | 19.3 | NA | 0.7 | 417 | NA |
| 1 | i.p. | 397 | 1.1 | 0.8 | 578 | 1.1 | |
| 10 | i.p. | 6120 | 24.7 | 1.8 | 2200 | 1.0 | |
| Wistar, male | 1 | p.o | 549 | 1.9 | 0.8 | 785 | 1.4 |
| 3 | i.p. | 649 | 5.76 | 1.6 | 534 | 2.87 |
NS9283 was administered rats i.p and p.o and plasma as well as brain concentrations were determined at various time points (n= 3 at each point (n= 2 for Wistar i.p.)) as described in the Methods section.
Maximal plasma concentrations (Cmax). Determined as the highest measured plasma concentration following i.p. or p.o. dosing.
Maximal brain concentrations (Cmax,brain). Determined as the highest measured brain concentration following i.p. or p.o. dosing and expressed as µmol·kg−1tissue.
AUC∞normalized to dose.
Brain-to-plasma distribution ratios (B/P) were determined as AUC∞,brain/AUC∞,plasma.
Brain concentration at 1 h time point.
Brain-to-plasma distribution ratio (B/P) was determined as Cbrain/Cplasma.